A phase II study of rucaparib in patients with high genomic LOH and/or BRCA 1/2 mutated stage IV non-small cell lung cancer (Lung-MAP Sub-Study, S1900A).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9024-9024
Author(s):  
Jonathan W. Riess ◽  
Mary Weber Redman ◽  
Paul Wheatley-Price ◽  
Bryan A. Faller ◽  
Liza C. Villaruz ◽  
...  
Keyword(s):  
Adverse Events ◽  
Systemic Therapy ◽  
Interim Analysis ◽  
Advanced Nsclc ◽  
Performance Status ◽  
Stage Iv ◽  
Eligibility Criteria ◽  
Phenotypic Marker ◽  
Platinum Based Chemotherapy ◽  
Grade 3

9024 Background: While prior studies have shown robust efficacy leading to FDA approval of PARP inhibitors (PARPi) in BRCA-associated cancers, data in NSCLC are much less clear. S1900A, a LUNG-MAP substudy, evaluated the PARPi rucaparib in advanced stage NSCLC harboring BRCA1/2 mutations or genomic loss of heterozygosity (LOH) as a phenotypic marker of homologous recombination deficiency (HRD). Methods: Eligible patients (pts) were required to have a deleterious mutation in BRCA1/BRCA2 and/or high (≥21%) genomic LOH. Key eligibility criteria: advanced NSCLC patients (pts) with progression on or after platinum based chemotherapy and/or PD-(L)1 antibody and progressed on most recent line of systemic therapy, a Zubrod performance status of 0-1, adequate organ function, no ≥ grade 3 hypercholesterolemia, no previous PARPi exposure and no systemic therapy within 21 days of registration. Pts stratified by histology into two cohorts (squamous [sq] and non-squamous/mixed histology [nsq]). With 40 eligible pts per cohort, the design had 91% power to rule out an ORR of 15% if the true ORR was at least 35% at the 1-sided 5% level. A planned interim analysis on the first 20 pts evaluable for response per cohort required ≥ 3 responses to proceed to full enrollment. Results: 64 pts enrolled (27 sq cohort; 37 nsq cohort) of whom 59 are eligible. Median age 65.7 yrs; M/F 33/26 (56/44%); 98% of the pts received at least 1 prior line of treatment for stage IV disease. Biomarker selection included 36 pts (61%) LOH only, 4 pts (7%) BRCA1 only, 11 pts (19%) BRCA2 only, 4 pts (7%) BRCA1 + LOH high and 4 pts (7%) BRCA2 + LOH high. Both cohorts were closed for futility with insufficient responses in the interim analysis populations. In the full study, 4 responses (3 nsq/1 sq) were reported. ORR was 7% (95% CI: 0-13) (9% nsq/4% sq) and DCR was 62% (95% CI: 50-75) (62% nsq/64% sq); 3 of the 4 responders harbored BRCA1/2 mutations and 1 of 4 high LOH; ORR in BRCA1/2+ pts 3/23 (13%). Median PFS was 3.2 months (95% CI: 1.6-4.6) in nsq cohort and 2.9 months (95% CI 1.6-6.2) in sq cohort. Median OS was 7.8 months in nsq cohort and 7.9 months in sq cohort. The most frequent grade ≥3 adverse events were anemia (22%), lymphopenia (8%), fatigue (8%) and transaminitis (5%). Conclusions: S1900A failed to show the requisite level of efficacy for rucaparib in advanced NSCLC pts with high genomic LOH and/or a BRCA1/2 mutation. There were no new safety signals and hematologic toxicities were the most frequent adverse events. Genomic LOH as a phenotypic marker of HRD does not predict sufficient activity of rucaparib in NSCLC. These results stand in contrast to the high level of efficacy of PARPi in patients with BRCA-associated or high LOH cancers of other tumor types. Underlying biologic differences in the genomic characteristics of these cancers vs. NSCLC may be responsible. Studies examining this premise are ongoing. (NCT03845296). Clinical trial information: NCT03845296.

Randomized phase III trial of gemcitabine and cisplatin versus gemcitabine alone in patients with advanced non-small cell lung cancer (NSCLC) and a performance status (PS) 2: CAPPA-2 study.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8066-8066
Author(s):  
Alessandro Morabito ◽  
Vittorio Gebbia ◽  
Saverio Cinieri ◽  
Maria Grazia Viganò ◽  
Roberto Bianco ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Performance Status ◽  
Single Agent ◽  
Stage Iv ◽  
Phase Iii ◽  
Line Treatment ◽  
First Line ◽  
Platinum Based Chemotherapy ◽  
Nsclc Patients ◽  
First Line Treatment

8066 Background: Platinum-based chemotherapy (CT) is the standard treatment for patients (pts) with advanced NSCLC, but the evidence of its efficacy among ECOG PS2 pts is weak, because these pts are usually excluded from clinical trials; concern exists about tolerability and feasibility of standard CT in these pts. No prospective randomized trial has tested the addition of cisplatin to single-agent CT in pts with advanced NSCLC and PS2. Methods: CAPPA-2 was a multicentre, randomized phase III study for first-line treatment of PS2 pts with advanced NSCLC. Patients, aged 18-70, were eligible if they had stage IV or IIIB with malignant pleural effusion or metastatic supraclavicular nodes (TNM VI ed.) and adequate organ function. Patients in standard arm received gemcitabine 1,200 mg/m2 dd1 and 8.Patients in experimental arm received cispaltin 60 mg/m2 d1 plus gemcitabine 1,000 mg/m2 dd1 and 8. All treatments were repeated q3w, up to 4 cycles, unless disease progression or unacceptable toxicity. Primary endpoint was overall survival (OS). To have 80% power of detecting hazard ratio (HR) 0.71, corresponding to an increase in median OS from 4.8 to 6.8 months, 285 deaths were required. Results: The study was stopped in June 2012 after the enrolment of 57 pts, due to the slow accrual and the report of positive results from a similar study. Median OS was 3.0 months with single-agent gemcitabine and 5.9 months with cisplatin + gemcitabine (HR 0.52, 95% CI 0.28-0.98, p=0.039). Combination CT produced longer PFS (median 1.7 vs. 3.3 months, HR 0.49, 95% CI 0.27-0.89, p=0.017) and higher response rate (4% vs. 18%, p=0.19), without substantial increase in toxicity. Conclusions: Addition of cisplatin to single-agent gemcitabine improves survival as first-line treatment of PS2 patients with advanced NSCLC. Clinical trial information: NCT00526643.

Use of a multi-drug regimen gemcitabine, 5-fluorouracil, irinotecan, cisplatin bevacizumab, docetaxel and cyclophosphamide (GFIP/BDC) for heavily pretreated epithelial ovarian (EOC), Fallopian tube (FT) and primary peritoneal (PP) cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e17073-e17073
Author(s):  
Melissa Schwartz ◽  
Samantha Cohen ◽  
Peter Remsen Dottino ◽  
Ann Marie Beddoe
Keyword(s):  
Adverse Events ◽  
Performance Status ◽  
Descriptive Analysis ◽  
Initial Response ◽  
Drug Regimen ◽  
Severe Neutropenia ◽  
Limiting Factor ◽  
Platinum Based Chemotherapy ◽  
Cytotoxic Treatment ◽  
Grade 3

e17073 Background: Despite initial response rates to standard platinum-based chemotherapy for EOC/FT/PP, the majority of patients relapse. The purpose of this study was to describe response and tolerability of GFIP/BDC, a modification of the G-FLIP regimen (Bruckner et al), in patients with persistent or recurrent EOC/FT/PP. Treatment consisted of a 2-day combination of gemcitabine 300mg, 5-fluorouracil 500mg/m2, irinotecan 20-30mg/m2, cisplatin 20mg/m2, bevacizumab 4mg/kg, docetaxel 20mg/m2, and cyclophosphamide 20mg/m2 administered every 14 days. Methods: A retrospective descriptive analysis of 20 patients from a single academic institution who received combination GFIP/BDC therapy from January 1, 2011 to August 31, 2016 for persistent or recurrent EOC/FT/PP. Toxicities were retrospectively graded using CTCAE v4.0. Results: Twenty patients were identified with a median age 57.5 years (range 32-71). 85% of patients were non-Hispanic white, 90% had cancer of high-grade serous histology, and all had a GOG performance status of 0-1. Patients had received a median of 3 prior regimens and 95% were platinum-resistant. Median number of cycles administered was 9 (range 3-48) and patients remained on treatment for a median of 5.1 months (range 1.5-24). Thirteen patients (65%) experienced a clinical response (1 complete, 12 partial) with a median duration of 5 months (range 1.5-20). Eight patients (45%) survived progression free for at least 6 months. Grade 3 adverse events were hematologic (5), constitutional (3), gastrointestinal (3), neurologic (2), and vascular (1). Grade 4 adverse events included severe neutropenia (1) and anaphylaxis (1). Thirteen patients (65%) experienced at least one grade 3/4 adverse event. Patients discontinued treatment due to disease progression 65% (13), toxicity 20% (4), patient preference 10% (2), and one patient (5%) is currently on treatment. Conclusions: Selected EOC/FT/PP patients who have failed multiple lines of conventional cytotoxic treatment may benefit from GFIP/BDC. Toxicity might be a limiting factor for administration.

Final safety results of BO17704 (AVAiL): A phase III randomized study of first-line bevacizumab (Bv) and cisplatin/gemcitabine (CG) in patients (pts) with advanced or recurrent nonsquamous non-small cell lung cancer (NSCLC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8039-8039
Author(s):  
V. Hirsh ◽  
R. Ramlau ◽  
J. von Pawel ◽  
P. Zatloukal ◽  
G. Vera ◽  
...  
Keyword(s):  
Adverse Events ◽  
Advanced Nsclc ◽  
Response Rate ◽  
Randomized Study ◽  
Locally Advanced ◽  
Safety Data ◽  
Final Analysis ◽  
Phase Iii ◽  
Platinum Based Chemotherapy ◽  
Grade 3

8039 Background: AVAiL, an international placebo-controlled phase III trial, showed that Bv-based therapy significantly improved PFS and response rate in patients with advanced/recurrent NSCLC. This report summarizes overall safety findings from AVAiL. Methods: AVAiL randomized 1,043 patients with untreated locally advanced, metastatic or recurrent non-squamous NSCLC to C 80mg/m2 (d1) and G 1,250mg/m2 (d1 and d8) q3w for up to 6 cycles plus either Bv 7.5mg/kg q3w (n=331 with safety data), Bv 15mg/kg q3w (n=329) or placebo (n=326). Bv/placebo was administered until disease progression. Primary endpoint was PFS; secondary endpoints included OS, response rate, and safety. Safety was measured using NCI-CTC version 3.0 criteria for adverse events (AEs). Results: At final analysis, the median/maximum duration of Bv therapy was 4.9/28.5 mo (Bv 7.5) and 4.3/23.4 mo (Bv 15). The most common AEs overall were hematological and gastrointestinal (GI), and occurred in similar proportions of pts in the Bv and placebo arms. Grade ≥3 AEs occurred in 80%, 83%, and 77% of pts in the Bv 7.5, Bv 15 and placebo arms, respectively. The most common grade ≥3 adverse events were hematological, mainly neutropenia and thrombocytopenia. Neutropenia was reported in 43% (Bv 7.5), 40% (Bv 15) and 34% (placebo) of pts. Grade ≥3 AEs of special interest included hypertension (7%, 9% and 2%), proteinuria (2%, 3% and 0%), bleeding (4%, 5% and 2%) and hemoptysis (0.5%, 1.2% and 1.3%). The incidence of grade 5 hemoptysis was low (0.9%, 0.9% and 0% of pts, respectively). The incidence of GI perforations (<1%), thromboembolic events (≤8%), CHF (≤1%) and wound healing complications (<1%) was low and similar between treatment arms. The incidence of serious AEs was 39%, 45% and 36% in the Bv 7.5, Bv 15 and placebo arms, respectively. No new safety signals were reported. Conclusions: After E4599, AVAiL further demonstrated the efficacy of Bv in combination with platinum-based chemotherapy in the treatment of advanced NSCLC. Final safety data confirm the well established and manageable safety profile of Bv-based therapy in pts with advanced NSCLC. [Table: see text]

Phase II study of bevacizumab in combination with cisplatin and docetaxel as first-line treatment of patients (p) with metastatic non-squamous non-small cell lung cancer (NSCLC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e19023-e19023
Author(s):  
N. Ferrer ◽  
M. Cobo ◽  
A. Paredes ◽  
M. Méndez ◽  
J. Muñoz-Langa ◽  
...  
Keyword(s):  
Phase Ii ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Median Number ◽  
Line Treatment ◽  
Eligibility Criteria ◽  
Platinum Based Chemotherapy ◽  
History Of ◽  
Grade 3 ◽  
Number Of Cycles

e19023 Background: Bevacizumab (B), in addition to platinum-based chemotherapy, is indicated for 1st-line treatment of p with advanced NSCLC other than predominantly squamous cell histology. B has been shown to improve progression free survival (PFS) and overall survival (OS) when combined with cisplatin/gemcitabine and carboplatin/paclitaxel, respectively. However, there are limited data on the safety and efficacy of B in combination with other widely used chemotherapy doublets for NSCLC. This is a single-arm, open- labeled, single-stage phase II trial of cisplatin (C), docetaxel (D) and B for NSCLC. Methods: Eligibility criteria: chemo- naïve, stage IIIB wet or IV, non-squamous NSCLC, PS 0–1, no brain metastases and no history of gross hemoptysis. P received D (75 mg/m2), C (75 mg/m2), and B (15 mg/kg iv) on day 1 every 3 weeks for up to 6 cycles, followed by B 15 mg/kg alone every 3 weeks until disease progression or toxicity. Primary endpoint: PFS. Results: 50 p were enrolled (enrollment completed): 24% female, median age 60 (36–74), PS 1: 64%, adenocarcinoma: 72%; stage IV: 92%. Two p did not start treatment. Median follow-up is 5.3 months (range 0–13.6). Median number of cycles of B was 7 (range 0–18). 56% completed 6 cycles of treatment; 24% received ≥ 12 cycles of B. Most frequent grade ≥ 3 toxicities: diarrhea (14.6%), fatigue (14.6%), dyspnea (9.8%), anorexia (4.9%), alopecia (4.9%), esophagitis (4.9%), constipation (4.9%), mucositis (12.2%), proteinuria (4.9%); hematological toxicities: neutropenia (22%), febrile neutropenia (9.8%), leucopenia (14.6%), lymphopenia (4.9%). Of interest, 41.5% developed grade <3 epistaxis and 17% hypertension (1 p grade 3). One p died due to hemoptysis. 46 p were evaluable for response: 29 PRs (ORR: 63%). 18 of 48 p have experienced progression or death with a median SLP of 7.8 months (95% CI: 6.6-NR). Median OS is 13.5 months (95% CI: 12.7–13.6; 81.2% p censored); 1-year survival is 83.9% (95% CI: 67.4%-92.5%). Conclusions: Treatment with C, D and B, followed by maintenance B in 1st line of advanced non-squamous NSCLC shows an acceptable toxicity profile and promising efficacy. Final results will be presented. [Table: see text]

CCTG BR.34: A randomized trial of durvalumab and tremelimumab +/- platinum-based chemotherapy in patients with metastatic (Stage IV) squamous or nonsquamous non-small cell lung cancer (NSCLC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9502-9502 ◽  
Author(s):  
Natasha B. Leighl ◽  
Scott Andrew Laurie ◽  
Glenwood D. Goss ◽  
Brett Gordon Maxwell Hughes ◽  
Martin R. Stockler ◽  
...  
Keyword(s):  
Adverse Events ◽  
Randomized Trial ◽  
Advanced Nsclc ◽  
Smoking Status ◽  
Objective Response ◽  
Stage Iv ◽  
First Line ◽  
Open Label ◽  
Platinum Based Chemotherapy ◽  
Significant Difference

9502 Background: First-line therapy for advanced NSCLC includes PD-1 checkpoint inhibitor (ICI) monotherapy, and in combination with chemotherapy. Combination ICI have also demonstrated better survival compared to chemotherapy (CM-227). In CCTG BR.34, we compared overall survival (OS) in patients with advanced NSCLC receiving first-line durvalumab plus tremelimumab (DT) with or without platinum doublet chemotherapy (CT). Methods: This international, open-label, randomized trial accrued 301 participants from Canada and Australia, with stage IV NSCLC, EGFR/ALK wildtype, ECOG PS 0/1. Patients were randomized to DT for 4 cycles or DT+CT (pemetrexed- or gemcitabine-platinum), with ongoing D or D + pemetrexed (non-squamous) maintenance until disease progression. Stratification factors included histology, stage IVA v. IVB and smoking status. The primary endpoint was OS; secondary endpoints included progression-free survival (PFS), objective response rate (ORR = CR + PR) and adverse events (AEs). Results: At a median follow up of 16.6 months, no significant difference in OS was seen between the two treatment arms, with a median OS of 16.6 months with DT+CT v. 14.1 months with DT, (estimated HR 0.88, 90% CI 0.67-1.16). PFS was significantly improved in the DT+CT arm (stratified HR 0.67, 95% CI 0.52-0.88; medians 7.7 v. 3.2 months). ORR was higher in the DT+CT arm, 28% v. 14%, (odds ratio 2.1, p=0.001). Preplanned subgroup analysis demonstrated no significant differences in treatment outcomes by plasma TMB (<20 v. ≥20 mut/Mb, Guardant OMNI), age, sex, or smoking status. There was a trend to improved OS with DT+CT in the subgroup with PD-L1 TPS≥50%, (HR 0.64, 95% CI 0.40-1.04, p=0.07). Plasma TMB<20 mut/Mb was associated with shorter survival in both treatment groups (HR 1.99, 95% 1.3-3.1). Toxicity was greater in the DT+CT arm, with grade≥3 adverse events in 82% v. 70%, (p=0.02), most commonly dyspnea, nausea and cough. The incidence of immune-related adverse events was similar between arms (colitis 11%, pneumonitis 6%, endocrinopathy 21%). Grade 5 events occurred in 2.7%, (5 with DT+CT, 3 with DT). Conclusions: The addition of CT to first-line DT did not improve OS in advanced NSCLC. CT+DT improved ORR and PFS, and was associated with greater toxicity. No differential effects were seen by PD-L1 TPS nor bTMB. These data suggest that adding chemotherapy to ICI may be beneficial in those with PD-L1 TPS >=50%, and warrant further analysis in independent datasets. Clinical trial information: NCT03057106 .

Nivolumab (NIVO) + ipilimumab (IPI) + 2 cycles of platinum-doublet chemotherapy (chemo) vs 4 cycles chemo as first-line (1L) treatment (tx) for stage IV/recurrent non-small cell lung cancer (NSCLC): CheckMate 9LA.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9501-9501 ◽  
Author(s):  
Martin Reck ◽  
Tudor-Eliade Ciuleanu ◽  
Manuel Cobo Dols ◽  
Michael Schenker ◽  
Bogdan Zurawski ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Interim Analysis ◽  
Advanced Nsclc ◽  
Performance Status ◽  
Randomized Study ◽  
Objective Response ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Ecog Performance Status

9501 Background: NIVO + IPI was shown to improve overall survival (OS) and durability of response vs chemo in 1L advanced NSCLC in CheckMate 227 Part 1, regardless of PD-L1 expression. We hypothesized that a limited course of chemo combined with NIVO + IPI could provide rapid disease control while building on the durable OS benefit seen with dual PD-1 and CTLA-4 inhibition. CheckMate 9LA (NCT03215706) is a phase 3 randomized study evaluating NIVO + IPI + 2 cycles chemo vs chemo in 1L stage IV/recurrent NSCLC. Methods: Adults with tx-naive, histologically confirmed stage IV/recurrent NSCLC, ECOG performance status 0–1, and no known sensitizing EGFR/ALK alterations were randomized 1:1 to NIVO 360 mg Q3W + IPI 1 mg/kg Q6W + chemo (2 cycles) (n = 361) or chemo (4 cycles) alone (n = 358), stratified by PD-L1 (< 1% vs ≥ 1%), sex, and histology (squamous vs non-squamous). Chemo was based on histology. Pts with non-squamous NSCLC in the chemo-only arm could receive optional pemetrexed maintenance. Pts were treated with immunotherapy until disease progression, unacceptable toxicity, or for 2 y. The primary endpoint was OS; the interim analysis using Lan–DeMets alpha spending function with O’Brien–Fleming boundary was planned at ~80% information fraction (ie, after observing ~322 total events). Secondary endpoints included progression-free survival (PFS) and objective response rate (ORR) by blinded independent central review, and efficacy by PD-L1 subgroups. Exploratory endpoints included safety/tolerability. Results: Baseline characteristics were balanced across arms. At a preplanned interim analysis (minimum follow-up 8.1 mo), OS was significantly prolonged with NIVO + IPI + chemo vs chemo (HR 0.69, 96.71% CI: 0.55–0.87; P = 0.0006); statistically significant improvements in PFS and ORR were seen. With longer follow-up (minimum 12.7 mo), NIVO + IPI + chemo vs chemo continued to provide longer OS; median 15.6 vs 10.9 mo (HR 0.66, 95% CI: 0.55–0.80); 1-y OS rates were 63 vs 47%. Clinical benefit was consistent across all efficacy measures in key subgroups including by PD-L1 and histology. Grade 3–4 tx-related adverse events were reported in 47 vs 38% of pts in the NIVO + IPI + chemo vs chemo arms, respectively. Conclusions: CheckMate 9LA met its primary endpoint: a statistically significant improvement in OS was observed with NIVO + NSCLC-optimized IPI + a limited course of chemo vs chemo (4 cycles) in 1L advanced NSCLC. No new safety signals were reported. Clinical trial information: NCT03215706 .

The efficacy of chemotherapy in the advanced NSCLC patients who failed with the treatment of EGFR-TKI

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e19078-e19078
Author(s):  
S. Zhou ◽  
S. Ren ◽  
L. Zhang ◽  
H. Sun ◽  
C. Zhou
Keyword(s):  
Progressive Disease ◽  
Advanced Nsclc ◽  
Performance Status ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Response Duration ◽  
Eligibility Criteria ◽  
And Performance ◽  
Tki Treatment ◽  
Egfr Tki

e19078 Background: EGFR-TKI such as gefitinib and erlotinib were used as standard 2nd/3rd line therapy in previously treated NSCLC. However, those who benefit from EGFR-TKI will inevitably progress from the disease. We reported the efficacy of chemotherapy(CT) in the advanced NSCLC pts failed with the previously 2nd/3rd line treatment of EGFR-TKIs. Methods: Eligibility criteria included advanced NSCLC pts who got disease control(included CR, PR or SD) initially from TKI therapy and then progressed, PS = 0–2, and normal fatal organ function. Pts received systemic CT (docetaxal, pemetrexed, gemicitabine, novelbine or combined with platinum agent) until disease progression or unacceptable toxicity. Results: 32 pts were enrolled from Oct 15 2007 to Nov 30 2008. Demographics: M 56.3%/F 43.7%; median age 56 y [range 34–72]; stage IV 100%; PS 0/1/2: 3 (9.4%)/22(68.8%)/7(21.8%); adenocarcinoma/non-adenocarcinoma 29(90.6%)/3(9.4%); EGFR-TKI treatment duration >6 m 20(62.5%) /< 6 m 12(37.5%); monotherapy 16 (50%)/ doublets 16 (50%). All pts were evaluable for efficacy; partial response in 5 cases (15.6%), stable disease in 21 cases(37.5%), progressive disease in 15 (46.9%) ( Table ). The response of CT was not related with gender, age, regimens, but these with TKI treatment > 6 m achieved a significantly better response than those < 6 m(p=0.01) and these with PS 0–1 got a marginally significantly better response than PS 2(p=0.095). The toxicity was acceptable. Median progression free survival was 3.4 months and it was not correlated with the gender, age and regimens, but PFS were significant longer in the pts received > 6 m of TKI (median 4.8 vs 1.9, p=0.009) and with PS 0–1 (median 4.7 vs 1.9, p=0.002). Conclusions: Pts benefited from TKI therapy and developed progressive disease could also benefit from CT. The response duration of EGFR-TKI and performance status could be predictive for the better efficacy of CT. [Table: see text] No significant financial relationships to disclose.

Safety of Vinflunine in Patients with Advanced Urothelial Carcinoma Refractory to Platinum-based Chemotherapy: A Prospective Pilot Study

2019 ◽  
Vol 14 (1) ◽  
pp. 31-36
Author(s):  
Raafat Abdel-Malek ◽  
Kyrillus S. Shohdy ◽  
Noha Abbas ◽  
Mohamed Ismail ◽  
Emad Hamada ◽  
...  
Keyword(s):  
Pilot Study ◽  
Adverse Events ◽  
Urothelial Carcinoma ◽  
Transitional Cell ◽  
Chemotherapeutic Agents ◽  
Serious Adverse Events ◽  
Platinum Based Chemotherapy ◽  
Number Of Patients ◽  
Advanced Urothelial Carcinoma ◽  
Grade 3

Background: Several single chemotherapeutic agents have been evaluated as the second-line treatment of advanced urothelial carcinoma. Despite encouraging efficacy outcomes, toxicity has often led to dose modifications or discontinuation. We aimed to assess the safety of vinflunine in a particular population of advanced transitional cell carcinoma of urothelium (TCCU), that were exposed to the previous toxicity of chemotherapy. Methods: This is an open-label, prospective, single-center pilot study to evaluate the response rate and safety profile of vinflunine in patients with advanced TCCU. It was planned to enroll 25 evaluable patients. Eligible patients are those with progressive disease after first-line platinum-based regimen for advanced or metastatic disease. Results: The study was prematurely closed due to two sudden deaths that were judged by the review board as treatment-related. Only ten patients were evaluated and received at least one cycle of vinflunine. All but one were male and seven underwent radical surgery. Eight had a distant metastasis (mainly lung and/or liver). Disease control rate was 40%, four patients had a partial response with median duration of response of 3.5 months. The median overall survival was 3.2 months (95% CI:1.67- 4.73). There were three serious adverse events namely two sudden deaths and one grade 4 thrombocytopenia. Nine grade 3/4 adverse events occurred. The most common all-grade adverse events were fatigue (50%), constipation (40%) and vomiting (40%). Moreover, grade 3 fatigue occurred in 30% of patients. Only one patient, who achieved PR for 5 months, was fit to receive further cytotoxic chemotherapy. Conclusion: The activity of vinflunine in advanced urothelial carcinoma came at the expense of its safety. The use of vinflunine has to be limited to the selected group of patients. However, this is a single institute experience in a limited number of patients.

Phase II study of docetaxel and cisplatin in advanced non-small-cell lung cancer.

1998 ◽  
Vol 16 (5) ◽  
pp. 1948-1953 ◽  
Author(s):  
J Zalcberg ◽  
M Millward ◽  
J Bishop ◽  
M McKeage ◽  
A Zimet ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Phase Ii ◽  
Advanced Nsclc ◽  
Response Rate ◽  
Phase Ii Study ◽  
Performance Status ◽  
Objective Response ◽  
Small Cell ◽  
Small Cell Lung ◽  
Grade 3

PURPOSE Docetaxel (Taxotere, Rhone-Poulenc Rorer, Antony, France) and cisplatin are two of the most active single agents used in the treatment of non-small-cell lung cancer (NSCLC). A recently reported phase I study of the combination of docetaxel and cisplatin recommended a dose of 75 mg/m2 of both drugs every 3 weeks for subsequent phase II study. PATIENTS AND METHODS Eligible patients were aged 18 to 75 years with a World Health Organization (WHO) performance status < or = 2 and life expectancy > or = 12 weeks, with metastatic and/or locally advanced NSCLC proven histologically or cytologically. Patients were not permitted to have received prior chemotherapy, extensive radiotherapy, or any radiotherapy to the target lesion and must have had measurable disease. Concurrent treatment with colony-stimulating factors (CSFs) or prophylactic antibiotics was not permitted. Docetaxel (75 mg/m2) in 250 mL 5% dextrose was given intravenously (i.v.) over 1 hour immediately before cisplatin (75 mg/m2) in 500 mL normal saline given i.v. over 1 hour in 3-week cycles. Premedication included ondansetron, dexamethasone, promethazine, and standard hyperhydration with magnesium supplementation. RESULTS A total of 47 patients, two thirds of whom had metastatic disease, were entered onto this phase II study. The majority of patients were male (72%) and of good (WHO 0 to 1) performance status (85%). All 47 patients were assessable for toxicity and 36 were for response. Three patients were ineligible and eight (17%) discontinued treatment because of significant toxicity. In assessable patients, the overall objective response rate was 38.9% (95% confidence limits [CL], 23.1% to 56.5%), 36.1% had stable disease, and 25% progressive disease. On an intention-to-treat analysis, the objective response rate was 29.8%. Median survival was 9.6 months and estimated 1-year survival was 33%. Significant (grade 3/4) toxicities included nausea (26%), hypotension (15%), diarrhea (13%), and dyspnea mainly related to chest infection (13%). One patient experienced National Cancer Institute (NCI) grade 3 neurosensory toxicity after eight cycles. Grade 3/4 neutropenia was common and occurred in 87% of patients, but thrombocytopenia > or = grade 3 was rare (one patient). Significant (grade 3/4) abnormalities of magnesium levels were common (24%). Febrile neutropenia occurred in 13% of patients and neutropenic infection in 11%, contributing to two treatment-related deaths. No neutropenic enterocolitis or severe fluid retention was reported. CONCLUSION Compared with other active regimens used in this setting, the combination of docetaxel and cisplatin in advanced NSCLC is an active regimen with a similar toxicity profile to other combination regimens.

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